1. Field of Invention
The present invention relates to a method for treatment of autoimmune diseases, such as organ specific and organ non-specific autoimmune diseases, AIDS, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis using rhamnolipids as the active ingredients in the treatment.
2. Description of the Background
Immune response
In immune responses, the ultimate target is an antigen, (bacterium or other invader). Antigen cells, such as macrophages, ingest antigens and fragment them into antigen peptides. Parts of these peptides join to form major histocompatibility complex (MHC) molecules and display themselves on the surface of the cell. T-Lymphocytes have receptors which can recognize a non-native peptides combined with MHC molecules. T-cells are activated and secrete lymphokines, or chemical signals, that mobilize other components of the immune system. Those cells are for the most part B-lymphocytes. B-lymphocytes recognize portions of antigens in various solutions of the body, in which the antigens are not combined with MHC molecules. T-cells cannot recognize the entire antigen. The receptors on T- cells recognize protein fragments of antigens, generally peptides composed of 8 to 15 amino acids.
Consequently, there are two kinds of immune response: (1) Humoral immunity, which occurs through action of B-cells; and (2) cell mediated immunity which occurs through T-cells.
In the case of viral infection, the virus might be able, through mutation, to change its outer envelope rapidly and thus prevent neutralization by antibodies. But when the virus contains proteins within its core that are essential for its life process, that mutation is not permitted. When the virus replicates inside cells, short peptide chains break off from the viral proteins and travel to the cell surface. They serve as ripe targets for the T-cells, which can then attack the infected cell and inhibit the spread of the virus, or as happens in autoimmune diseases, to attack the cells of the body.
T-cells themselves comprise two subpopulations, CD4 (helper) and CD8 (killer) cells. Each type of T-cell uses its own form of MHC to make peptides recognizable. After CD4 cells receive the proper chemical signal, they produce large amounts of lymphokines to accelerate the division of other T-cells. Activated CD8 cells produce much smaller amounts of lymphokines but develop the capacity to punch holes into target cells and to secrete chemicals that kill infected cells or cells which have been in some other way changed.
Autoimmune diseases
Autoimmune diseases occur when T-lymphocytes become activated upon recognizing self antigen linked to the autologous class II molecule of the MHC. One of the key features of autoimmune diseases is that the immune system does not distinguish the body's own components from those of foreign invader's, and thus the body's immune system turns against itself. Genetic factors are obvious contributors as found from studies of identical twins. In the case of multiple sclerosis it has been shown that when one twin gets multiple sclerosis, the other twin has about a 30% chance of acquiring it.
There is also a tendency for more than one autoimmune disorder to occur in the same individual. When this happens, the association is often between diseases within the same region of the autoimmune spectrum. For example, patients with autoimmune thyroiditis have a much higher incidence of pernicious anemia than would be expected from examination of a random population matched for age and sex.
Autoimmune phenomena also tend to aggregate along family lines. It has been shown that the subjects with Hashimoto's disease or pernicious anemia show a high incidence of thyroid and gastric autoantibodies in their first degree relatives. Going from strictly organ specific to less organ specific autoimmune diseases there is a spectrum of autoimmune illnesses as shown below.
Spectrum of Organ Specific Autoimmune Diseases
In descending order, from organ specific to organ non-specific, the list of autoimmune diseases includes: Hashimoto's thyroiditis, Primary myxedema, Thyrotoxicosis, Pernicious anemia, Autoimmune atrophic gastritis, Addison's disease, Premature menopause, Male infertility, Juvenile diabetes, Goodpasture's syndrome, Sympathetic ophthalmia, Phagogenic uveitis, Multiple sclerosis, Psoriasis, Autoimmune hemolytic anemia, Idiopathic thrombocytopenic purpura, Idiopathic leucopenia, Primary biliary cirrhosis, Active chronic hepatitis HBs-ve, Cryptogenic cirrhosis, Pemphygus vulgaris, Ulcerative colitis, Sjogren's syndrome, Poststreptococcal glomerulonephritis, Rheumatoid arthritis, Scleroderma, Wagener's granulomatosis, and Poly/dermatomyositis.
Most of the state of the art approaches to treatment of these diseases involve manipulation of immunological responses. However, in many organ-specific diseases, metabolic control is usually sufficient, such as thyroxine replacement in primary myxedema, insulin in juvenile diabetes, vitamin B12 in pernicious anemia, anti-thyroid drugs for Grave's disease, acetylcholinesterase in myasthenia gravis, thymectomy, steroids in systematic lupus erythematosus and immune complex nephritis, and steroids plus anti-inflammatory drugs like salicylates penicillamine, gold salts in rheumatoid arthritis etc. The efficacy of Cyclosporin A has been proven in such diseases as uveitis, early type I diabetes, nephrotic syndrome and psoriasis, idiopathic thrombocytopenic purpura, systematic lupus erythematosus, polymyositis, Chron's disease, primary biliary cirrhosis, myasthenia gravis, and refractory rheumatoid arthritis.
Some studies suggest that the target for treatment of autoimmune diseases could be the resulting complex of antigen/MHC/T-cell receptor using specific antibodies. Allergic encephalomyelitis is an acute neurological autoimmune disease which is widely regarded as a model for autoimmune disorders and which is mediated by CD4+ T-cells recognizing myelin basic protein (BP), or its peptides, in association with self I-a. Studies have been reported using monoclonal antibodies in treating allergic encephalomyelitis. These monoclonal antibodies bound only the complex of BP and I-as. In vitro, they blocked the proliferative response to the encephalitogenic determinant of BP and reduced the response to intact BP, without affecting the response to a non-relevant antigen-purified protein derivative of tuberculin presented on syngeneic macrophages. They also inhibited experimental allergic encephalomyelitis in H-2s mice. (Aharoni, R; Nature 1991, 351 (6322))